Metal-on-Metal Hip Joint Prostheses: a Retrospective Case Series Investigating the Association of Systemic Toxicity with Serum Cobalt and Chromium Concentrations.

INTRODUCTION: There have been concerns about prosthesis failure and the potential for systemic toxicity due to release of cobalt and chromium from metal-on-metal hip joint prostheses (MoM-HP). There is conflicting evidence on whether there is a correlation between higher cobalt and chromium concentrations and systemic toxicity. METHODS: We undertook a retrospective review of consecutive patients with MoM-HP referred for outpatient review in toxicology clinics in London, UK, and in the USA recorded in the Toxicology Investigators Consortium (ToxIC) Registry from June 2011 to June 2015. RESULTS: Thirty-one cases were identified; the median (IQR) serum cobalt concentration was 10.0 (3.8-32.8) mcg/L, and the median (IQR) serum chromium concentration was 6.9 (3.7-18.7) mcg/L. Twenty-three (74.2%) had symptoms, most commonly lethargy, hearing loss, and tinnitus. The odds ratios of symptomatic/asymptomatic patients for metal ion concentrations above/below 7 mcg/L were 1.87 (95% CI 0.37-9.57, p = 0.45) and 0.60 (95% CI 0.10-3.50, p = 0.57) for cobalt and chromium, respectively. Two (6.5%) patients with systemic cobalt toxicity had median (IQR) serum cobalt concentrations significantly higher than those without systemic features (630.4 [397.6-863.2] mcg/L versus 9.8 [2.9-16.4] mcg/L; p = 0.017). However, overall, there were no differences between cobalt (p = 0.38) or chromium (p = 0.92) concentrations between symptomatic and asymptomatic patients and no clinical features or investigation results correlated with cobalt or chromium concentration. CONCLUSION: Two (6.5%) of 31 individuals referred for assessment of MoM-HP were diagnosed with systemic cobalt toxicity. However, despite a high prevalence of reported symptoms, neither symptoms nor investigation results correlated with serum cobalt or chromium concentrations.

Cobalt(II) Chloride Modifies the Phenotype of Macrophage Activation.

Cobalt (Co) is vital for cells in trace amounts, but excessive exposure to Co is possible due to surgical devices such as artificial metal-on-metal joints. Cobalt(II) chloride (CoCl2 ) has also been shown to imitate hypoxic conditions in cells by stabilizing the transcription factor hypoxia-inducible factor-1α (HIF-1α). The purpose of this study was to investigate the possible immunomodulatory action of CoCl2 by investigating its effects on the expression of inflammatory genes in macrophages. The following factors were assessed: inducible nitric oxidase synthase (iNOS), nicotinamide adenine dinucleotide phosphate-oxidase 2 (NOX2), interleukin-6 (IL-6), arginase-1 and HIF-1α. In the absence of exogenous cytokines, CoCl2 enhanced alternative (M2) macrophage activation as demonstrated by increased arginase-1 expression, but had no direct effect on inflammatory factors associated with classical (M1) activation. Interestingly, in lipopolysaccharide (LPS)-stimulated macrophages, CoCl2 modified the M1-type activation profile by increasing iNOS expression and nitric oxide production and decreasing NOX2 and IL-6. Also, CoCl2 increased HIF-1α levels in unstimulated and LPS-stimulated cells as expected. In conclusion, we showed that CoCl2 enhanced alternative (M2) activation in resting macrophages. In addition, CoCl2 was found to remodel the classical M1 phenotype of macrophage activation by changing the balance of iNOS, NOX2 and IL-6.

Cobalt toxicity after revision total hip replacement due to fracture of a ceramic head. / Toxicidad por cobalto después de la revisión a una artroplastia total de cadera posterior a fractura de cabeza cerámica.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare, but devastating complication. Potential clinical findings include cardiomyopathy, hypothyroidism, skin rash, visual and hearing impairment, polycythaemia, weakness, fatigue, cognitive impairment, and neuropathy. The case is presented of a 74year-old man in whom, after a ceramic-ceramic replacement and two episodes of prosthetic dislocation, it was decided to replace it with a polyethylene-metal total hip arthroplasty (THA). At 6months after the revision he developed symptoms of cobalt toxicity, confirmed by analytical determination (serum cobalt level=651.2µg/L). After removal of the prosthesis, the levels of chromium and cobalt in blood and urine returned to normal, with the patient currently being asymptomatic. It is recommended to use a new ceramic on ceramic bearing at revision, in order to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Systemic effects of cobalt toxicity after revision hip replacement can manifest in intermediate to long term follow-up.

INTRODUCTION: Metal toxicity from metal-on-metal hip replacements is now well documented and several large series have reported local reactions. Although less common, there are reports of similar reactions from failed ceramic liners. Systemic effects documented in literature have been grouped into cardiac, neuro-ocular and thyroid signs. METHODS AND RESULTS: We report a case of a patient who had revision for fractured ceramic liner to metal on polyethylene. Third body effect of the ceramic particles led to wear through of the poly liner and the head directly articulating with metal shell. He developed cardiac and neurological features of cobalt toxicity in addition to extensive soft tissue destruction. Revision of the bearing surfaces and synovectomy led to clinical improvement and fall in metal ion levels. CONCLUSIONS: We recommend 2-stage revision in such situations and close monitoring of all these patients.

Progressive Cardiomyopathy in a Patient With Elevated Cobalt Ion Levels and Bilateral Metal-on-Metal Hip Arthroplasties.

Systemic cobalt toxicity is a rare complication after metal-on-metal (MOM) total hip arthroplasty. Here we present a case of progressive cardiomyopathy, as evidenced by biopsy and cardiac magnetic resonance imaging (MRI), in a patient with bilateral MOM total hip arthroplasties. To our knowledge, it is one of the first cases in which cardiomyopathy resulting from systemic cobalt disease has been shown on MRI. While there is no guideline to unequivocally diagnose cobalt cardiomyopathy, the constellation of findings, including pathologic, biologic, blood levels, imaging, and surgical, all uniformly indicate a unifying diagnosis. The lack of improvement after removal of the prosthetic device supports a diagnosis of permanent myocardial damage, which is consistent with cardiomyopathy of advanced toxic etiology.

["Why am I Deaf and my Vision is Blurred?" Thinking of a Horse or a Zebra?]. / "Warum sehe und höre ich immer schlechter?".

We present the case of a 66 year old patient with a heterogeneous clinical course over ten months, particularly worsening of vision, hearing and hip pain. She finally died of multi-organ failure. The increased wear of a metal-on-metal hip implant lead to cobalt intoxication. The crucial therapy consists in removing the cobalt source. In the future, physicians need to be aware of this insidious and life-threatening disease possibly affecting thousands of patients after total hip replacement.

[Effect of L-carnitine, afobazole and their combination with L-arginine on biochemical and histological indices of endothelial disfunction in cobalt intoxication in rats].

The influence of L-carnitine and afobazole and their combination with L-arginine on biochemical and histological indices of endothelial dysfunction in rats with cobalt intoxication. The obtained data revealed biochemical markers of endothelial dysfunction. Found that-in rats with cobalt intoxication during treatment occurred inhibition of lipid peroxidation (LPO), reduced the concentration of malondialdehyde (MDA) in erythrocytes, activation of superoxide dismutase (SOD). This was accompanied by increased concentrations of nitric oxide (NO), the availability of the substrate L-arginine and possibly the expression of eNOS in the background of L-carnitine and afobazole.

Intolerability of cobalt salt as erythropoietic agent.

Unfair athletes seek ways to stimulate erythropoiesis, because the mass of haemoglobin is a critical factor in aerobic sports. Here, the potential misuse of cobalt deserves special attention. Cobalt ions (Co(2+) ) stabilize the hypoxia-inducible transcription factors (HIFs) that increase the expression of the erythropoietin (Epo) gene. Co(2+) is orally active, easy to obtain, and inexpensive. However, its intake can bear risks to health. To elaborate this issue, a review of the pertinent literature was retrieved by a search with the keywords 'anaemia', 'cobalt', 'cobalt chloride', 'erythropoiesis', 'erythropoietin', 'Epo', 'side-effects' and 'treatment', amongst others. In earlier years, cobalt chloride was administered at daily doses of 25 to 300 mg for use as an anti-anaemic agent. Co(2+) therapy proved effective in stimulating erythropoiesis in both non-renal and renal anaemia, yet there were also serious medical adverse effects. The intake of inorganic cobalt can cause severe organ damage, concerning primarily the gastrointestinal tract, the thyroid, the heart and the sensory systems. These insights should keep athletes off taking Co(2+) to stimulate erythropoiesis.

Clinical features, testing, and management of patients with suspected prosthetic hip-associated cobalt toxicity: a systematic review of cases.

Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations.

Prosthetic hip-associated cobalt toxicity.

Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist.

Systemic disease after hip replacement: aeromedical implications of arthroprosthetic cobaltism.

BACKGROUND: A multisystem illness recently reported in recipients of the newest generation of metal-on-metal hip prostheses has been ascribed to toxic effects of cobalt and possibly chromium. CASE REPORT: We present a case of insidiously developing neurologic illness that occurred in a physically active professional. DISCUSSION: This case illustrates the potential for a hip prosthesis to occultly impair safe functioning of aviators. Based on this case and others, we suggest modifications to aeromedical policy relating to waiver requests after hip replacement, including routine monitoring of serum cobalt and chromium levels in recipients of metal-on-metal hip prostheses. The evaluation of aviators having an elevated cobalt level is also discussed.

Fatal cardiomyopathy after revision total hip replacement for fracture of a ceramic liner.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare but devastating complication. It has been reported following revision of fractured ceramic components, as well as in patients with failed metal-on-metal articulations. Potential clinical findings include fatigue, weakness, hypothyroidism, cardiomyopathy, polycythaemia, visual and hearing impairment, cognitive dysfunction, and neuropathy. We report a case of an otherwise healthy 46-year-old patient, who developed progressively worsening symptoms of cobalt toxicity beginning approximately six months following synovectomy and revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. The whole blood cobalt levels peaked at 6521 µg/l. The patient died from cobalt-induced cardiomyopathy. Implant retrieval analysis confirmed a loss of 28.3 g mass of the cobalt-chromium femoral head as a result of severe abrasive wear by ceramic particles embedded in the revision polyethylene liner. Autopsy findings were consistent with heavy metal-induced cardiomyopathy.We recommend using new ceramics at revision to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

[Cobalt poisoning due to metal-on-metal hip implants]. / Kobaltvergiftiging door metaal-op-metaalheupprothese.

Since 2011, cobalt and chromium blood levels are measured in patients with a metal-on-metal hip implant (MoM prosthesis). In this article we discuss the health risks that are related to chronically elevated blood cobalt concentrations induced by abnormal wear and corrosion of the MoM prosthesis. Only a few patients who have systemic symptoms of poisoning, besides local symptoms around the failing MoM prosthesis, have been described in the literature. Toxic blood cobalt concentrations may be accompanied by hypothyroidism, polyneuropathy, impairment of cranial nerves II and VIII and cardiomyopathy. Treatment consists of removal of the prosthesis. In patients with a normal kidney function, the cobalt blood levels rapidly decrease and symptoms of cobalt intoxication subside. Chelation therapy should be restricted to those patients who are unable to undergo removal of the prosthesis immediately due to their medical condition. This can for example be because of a severe cobalt-induced cardiomyopathy.

[The hard lesson of metal-on-metal hip implants]. / De harde les van metaal-op-metaalheupprothesen.

Metal-on-metal hip implants with a large metal head (≥ 36 mm) have shown periprosthetic adverse soft tissue reactions and high blood concentrations of metal ions in patients. This has raised concern that exposure to metal ions may induce complications and could increase the risk of cancer. In view of the present level of uncertainty and for reasons of patient safety, the Dutch Orthopaedic Association (NOV) has advised its members to suspend utilisation of all metal-on-metal hip implants with a large head (≥ 36 mm) until the safety and long-term effectiveness have been established. All patients with these implants will be invited for an annual check-up according to a set protocol. This outpatient examination will also include assessment of cobalt ion levels and X-ray diagnostics. Based on the blood concentration of cobalt, the clinical status and the X-ray, the patient will be advised to undergo a revision procedure of the implant.

Severe cobalt intoxication following hip replacement revision: clinical features and outcome.

CONTEXT: Cobalt intoxication has become more frequent due to the wide use of metal hip implants. CASE DETAILS: A 56-year-old male patient underwent total hip prosthesis, with a ceramics-on-ceramics implant. Almost 3 years later, it was replaced by metal implant containing cobalt, chromium, and titanium. He developed weight loss, heart, thyroid, and neurological toxicity, with severe hearing loss. He was treated with 2,3-dimercaptopropane-1-sulfonate (DMPS), and cobalt excretion increased. Clinical symptoms apart from deafness gradually resolved. CONCLUSION: We report significant cobalt poisoning from a damaged hip replacement with cobalt containing implant and a slow abrasion of the metal by residual ceramic particles. Chelation therapy resulted in apparent benefit.